miR-9 regulates basal ganglia-dependent developmental vocal learning and adult vocal performance in songbirds
Abstract
miR-9 is an evolutionarily conserved miRNA that is abundantly expressed in Area X, a basal ganglia nucleus required for vocal learning in songbirds. Here, we report that overexpression of miR-9 in Area X of juvenile zebra finches impairs developmental vocal learning, resulting in a song with syllable omission, reduced similarity to the tutor song, and altered acoustic features. miR-9 overexpression in juveniles also leads to more variable song performance in adulthood, and abolishes social context-dependent modulation of song variability. We further show that these behavioral deficits are accompanied by downregulation of FoxP1 and FoxP2, genes known to be associated with language impairments, disruption of dopamine signaling, and widespread changes in expression of genes important in circuit development and functions. These findings demonstrate a vital role for miR-9 in basal ganglia function and vocal communication, suggesting that dysregulation of miR-9 in humans may contribute to language impairments and related neurodevelopmental disorders.
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Author details
Funding
National Institute of Mental Health (R01MH105519)
- XiaoChing Li
National Science Foundation (1258015)
- XiaoChing Li
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocol (#3187) of the LSU School of Medicine.
Copyright
© 2018, Shi et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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